Effects of ryanodine receptor activation on neurotransmitter release and neuronal cell death following kainic acid-induced status epilepticus

详细信息    查看全文

• 作者：Fumiaki Mori ; Motohiro Okada ; Masahiko Tomiyama ; Sunao Kaneko and Koichi Wakabayashi
• 关键词：Ryanodine receptor ; Inositol 1 ; 4 ; 5-trisphosphate receptor ; Kainic acid ; Neuronal cell death ; In situ hybridization
• 刊名：Epilepsy Research
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：65
• 期：1-2
• 页码：59-70
• 全文大小：583 K

文摘

Dynamic changes in intracellular free Ca²⁺ concentration play a crucial role in various neural functions. The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) and the ryanodine (Ry) receptor (RyR) are involved in Ca²⁺-induced Ca²⁺-release (CICR). Recent studies have shown that type 3 IP3R is highly expressed in rat hippocampal neurons after kainic acid (KA)-induced seizures and that dantrolene, a RyR antagonist, reduces KA-induced neuronal cell death. We investigated the RyR-associated effects of CICR agents on basal and K⁺-evoked releases of GABA and glutamate in rat hippocampus and the changes in expression of mRNA for RyRs in mouse brain after KA-induced seizures. The stimulatory effect of Ry on releases of GABA and glutamate was concentration-dependent in a biphasic manner. The inflection point in concentration–response curves for Ry on GABA release was lower than that for glutamate in both basal and K⁺-evoked conditions, suggesting that hyperactivation of RyR-associated CICR produces the imbalance between GABAergic and glutamatergic transmission. Following KA-induced seizures, transient up-regulation of brain-type RyR mRNA was observed in the hippocampal CA3 region and striatum, and signals for c-Fos mRNA increased transiently in the hippocampus, dentate gyrus and deeper layers of the neocortex. Thereafter, some dead neurons with single-stranded DNA (ssDNA) immunoreactive fragmented nuclei appeared in these areas. These findings suggest that intracellular Ca²⁺ release via the RyR might be one of the mechanisms involved in KA-induced neuronal cell death.